From pediatric covariate model to semiphysiological function for maturation: part I-extrapolation of a covariate model from morphine to Zidovudine

Pharmacolog

From pediatric covariate model to semiphysiological function for maturation: Part I-extrapolation of a covariate model from morphine to zidovudine

New approaches to expedite the development of safe and effective pediatric dosing regimens and first-in-child doses are urgently needed. Model-based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covariate model for the glucuronidation of morphine into a pediatric population model for zidovudine glucuronidation. This model was compared with a reference model that gave the statistically best description of the data. Both models had adequate goodness-of-fit plots and normalized prediction distribution errors (NPDE), similar population clearance values for each individual, and a Δobjective function value of 13 points (Δ2df). This supports our hypothesis that pediatric pharmacokinetic covariate models contain system-specific information that can be used as semiphysiological functions in pediatric population models. Further research should explore the validity of the semiphysiological function for other UDP-glucuronosyltransferase 2B7 substrates and patient populations and reveal how this function can be used for pediatric physiologically based pharmacokinetic models

Экспериментальное изучение влияния глюкозамина гидрохлорида на развитие патоспермии стареющих крыс, вызванной доксорубицином

ГЛЮКОЗАМИНА ГИДРОХЛОРИДДОКСОРУБИЦИНПАТОСПЕРМИЯСТАРЕНИЕФАРМАКОЛОГИЯ КЛИНИЧЕСКАЯЛЕКАРСТВ ФИЗИОЛОГИЧЕСКОЕ ДЕЙСТВИЕРЕПРОДУКЦИЮ КОНТРОЛИРУЮЩИЕ СРЕДСТВАЭКСПЕРИМЕНТЫ НА ЖИВОТНЫХКРЫСЫЦель работы - исследование влияния глюкозамина гидрохлорида на развитие гипофункции семенников крыс, вызванной длительным введением доксорубицина на фоне старения животных

Statins in aortic disease

Background: Numerous studies indicate that statins have multiple beneficial actions (known as ‘plei-otropic actions’) on cardiovascular system through the improvement of endothelial dysfunction, inflammation, oxidative stress, excessive arterial thrombosis, and stabilization of the atherosclerotic plaque. Aortic disease primarily consists of aortic valve stenosis, aortic valve regurgitation, aneurysm disease, and genetic disorders such as Marfan syndrome, bicuspid aortic valve and aortic coarctation. Many studies have revealed the cardioprotective actions of statins in aortic disease. Objective: Our aim was to present current data concerning the value of treatment with statins in aortic diseases. Methods: A thorough search of PubMed and the Cochrane Database was conducted to identify the studies and novel articles related to the use of statins in aortic disease. Results: Numerous studies in animals and humans indicate a beneficial effect of treatment with statins in the previous conditions apart from a few conflicting data. Conclusion: There is a need of further investigation in this field, especially for the estimation of the optimal type and dose of statins required in each clinical condition of aortic disease. © 2017 Bentham Science Publishers

The predictive role for ST2 in patients with acute coronary syndromes and heart failure

Intensive research has shed light on the utilization of novel biomarkers which fa-cilitate the diagnosis and prognosis of patients with different medical problems. One of the most important biomarkers especially in the spectrum of heart failure is soluble ST2 (sST2: soluble Suppression of Tumorigenicity 2), which is involved in inflammation, fibrosis and cardiac stress. In the revised 2017 ACC/AHA/HFSA, “Focused Update Guidelines for the Management of Heart Failure” ST2 was given a class-IIa recommendation for the optimal risk assessment in patients with heart failure. Many studies indicate that not only baseline but also serial measurements of ST2 can accurately predict future cardiovascular events in pa-tients with Acute Coronary Syndromes and heart failure. Therefore, in this review, we are going to discuss the studies about the prognostic significance of ST2 in patients with Acute Coronary Syndromes, acute and chronic heart failure. © 2020 Bentham Science Publishers

Coronary artery disease and endothelial dysfunction: Novel diagnostic and therapeutic approaches

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction. © 2020 Bentham Science Publishers